3-hydroxypyrido [2, 3-e]-as-triazine 1-oxide and related compounds



United States Patent 3,108,102 3-HYDROXYPYRIDO[2,3-e]-as-TRIAZ1NEl-OXIDE AND RELATED COMPOUNDS John Anthony Carbon, Lake Bluif, IlL,assignor to Abbott Laboratories, North Chicago, 111., a corporation ofIllinors No Drawing. Filed Feb. 8, 1962, Ser. No. 171,805 4 Claims. (Cl.260-42495) This invention is concerned with compounds of the formulaadmixed with Water in the presence of a catalyst such as an alkali metalcarbonate, preferably potassium carbonate, to obtain the intermediateS-amino derivative of the formula l-NH: N N

which is thereafter reacted at about 20 C. with an alkali metal nitritein an acidified aqueous medium. The products are crystalline, yellowsolids and can be readily separated by filtration and recrystallizedfrom a suitable solvent or by dissolving in alkali and acidifying withan acid such as acetic acid.

The examples which follow are intended to illustrate rather than limitthe invention.

EXAMPLE 1 3-H ydroxypyrzdo [2,3-e] -as-Triazine 1 -0xide A mixture of 5g. of 2-guanidino-3-nitropyridine hydrochloride, g. of potassiumcarbonate and 50 ml. of water was heated on the steam bath with vigorousstirring for 6.5 hours. The reaction mixture was then cooled to 5 C. toprecipitate the intermediate 3-arninopyrido [2,3-e1-as-triazine l-oxidewhich after separation by filtration and recrystallization from watermelted at 256- 257 C. with decomposition and analyzed 43.03% nitrogencompared to the calculated value of 42.94% ni- 3*,l%8,l2 Patented Oct.22, 19:63

trogen. A solution of 50 g. (0.31 mole) of this intermediate in 560 ml.of water and ml. of concentrated sulfuric acid was cooled to 20 C. and asolution of 31.5 g. (0.46 mole) of sodium nitrite in 60 ml. of waterslowly added with stirring over a 30 minute period. After standing forone hour at room temperature, the desired 3-hydroxypyrido-[2,3-e1as-triazine l-oxide which precipitated from the reaction mixture waspurified by dissolving it in aqueous alkali and acidifying with aceticacid. M.P.=235237 C. with decomposition. N (calcd)=34.15%; N(found)=34.03%.

EXAMPLE 2 -By substituting 2-guanidino-3-nitro-S-rnethylpyridine for the2-guanidino-3-nitropyridine in the procedure of Example 1, there isobtained the intermediate 3-amino-7- methylpyrido[2,3-e]-as-triazinel-oxide melting at 267 268 C. which when further reacted with potassiumnitrite yields 3-hydroxy-7-rnethylpyrido[2,3-e]-as-triaz.ine 1- oxidemelting at 230-23 1 C. with decomposition.

The reaction of aqueous alkali with 2-guanidino-3-nitro-S-ethylpyridine,2 guanidino 3 nitro 5 propylpyridine orZ-guanidino-nitro-5-butyipyridine results in the formation of theintermediate 3-amino-7-ethylpyrido- 2,3e]-as-triazine l-oxide,3-amino-7-propylpyrido[2,3- e]-as-triaz'ine l-oxide or3-amino-7-butylpyrido[2,3-e]-astriazine l-oxide respectively which whenreacted with an alkali metal nitrite produces 3-hydroxy-7-ethylpyrido-[2,3-eJ-as-triazine l-oxide, 3-hydroxy7-propylpyrido [2,3-e]-as-triazine l-oxide, or 3-hydroxy-7-butyl pyrido[2,'3-e]- as-triazinel-oxide, respectively.

EXAMPLE 3 The substitution of 2-quanidino-3-nitro-5-chloropyridine for2-quanidino-3-nitropyridine in Example 1 results in the production ofthe intermediate 3-amino-7-ch1oropyrido[2,3-e]-as-triazine l-oxidemelting at 260 C. with decompoistion which when reacted with sodiumnitrite produces 3-hydroXy-7-chloropyrido[2,3-e1-as-triazine loxidehaving a molecular weight of 198.

The reaction of aqueous alkali with Z-iguanidino-S- nitro 5bromopyridine, 2 guanidino 3 nitro 5- fiuoropyridine or2-guanidino-3-nitro-5-iodopyridine will produce the intermediate3-amino-7-bromopyrido[2,3-e1- as-triazine 1-oxide,3-amino-7-fluoropyrido[2,3-e1-as-triazine l-oxide or3-amino-7-iodopyrido[2,3-e1-as-triazine l-oxide, respectively. Thereaction of these intermediates with sodium nitrite provides the desired3-hydroxy-7- bromopyrido[2,3-e1-triazine l-oxide,3-hydroxy-7-fluoropyrido[2,3e]-as-triazine l-oxide or3-hydroxy-7-iodopyrido[2,3-e] -as-triazine l-oxide, respectively.

Compounds of the formula \N/NH (I? NE:

NH employed as starting materials in this invention are prepared byrefiuxing two parts of guanidine with one part of a compound of theformula R NO:

3 in t-butyl alcohol and separating the solid product which forms. Thus,2-guanidino-4-nitropyridine melts at 143- 144 C. whereasZ-guanidino-B-nitro-5-methylpyridine melts at -145l47 C. and2-guanidin0-3-nitro-5-ohlor0- pyridine melts at 134-13S C.

What I claim is: 1. A compound of the formula 4 wherein R is a member ofthe group consisting of hydrogen, lower alkyl and halogen.

2. 3-hydroxypyrido[2,3--]-as-triazine l-oxide. 3.3-hydroxy-7-methylpyrido[2,3-e]-as-triazine l-oxide. 5 4.3-hydroxy-7-chloropyrido[2,3-e]-as-triazine l-oxide.

References Cited in the file of this patent Erickson et 21.: The 1,2,3-and 1,2,4-Triazines, Tctra zines and Pentazines, Interscience Pub. Inc.,New York, 10 1956, pages 101-103.

1. A COMPOUND OF THE FORMULA